The term indolent in describing a non-Hodgkin's lymphoma (NHL) generally refers to a group of B-cell NHLs composed of predominantly small cells that make up several categories, including follicular lymphoma, small lymphocytic lymphoma, and lymphoma of mucosa-associated lymphoid tissue. Most patients with follicular lymphoma respond to therapy, and the average survival time in large series is approximately 10 years. Patients who achieve a complete remission with initial treatment have an approximately 25% chance of remaining free of disease for 10 years. However, this means that more than 80% of patients will require salvage therapy. Cladribine is a newer purine analogue and is of particular interest because it is resistant to deamination by adenosine deaminase. It is cytotoxic to both proliferating and resting lymphocytes, making it an attractive agent for the treatment of indolent NHL. In this review article, we summarize the current treatment approaches for indolent NHL and the results of cladribine monotherapy studies in Japan and cladribine studies in Germany that have focused on a combination therapy with mitoxantrone. Cladribine is a potent inhibitor of DNA repair. The combination of a DNA-damaging agent with an inhibitor of DNA repair constitutes the rationale for combining cladribine with mitoxantrone. A German study has demonstrated that the combination of reduced-dose cladribine and mitoxantrone is a highly active regimen with favorable toxicity profiles. Cladribine is highly effective as a single agent and in combination with mitoxantrone in the treatment of indolent NHL, and its availability broadens the range of therapeutic options for indolent NHL.